A quarter of patients enrolled in the trial had objective responses or prolonged stable disease when treated with the anti-PD-1 antibody BMS-936558. Responses lasted for 1.9 to 30.8 months, were observed at all three doses evaluated, and occurred in patients with squamous and nonsquamous histology.

Analysis of pretreatment tumor samples provided evidence that PD lymphocyte-1 (PD-L1) expression correlated with response to the monoclonal antibody, said Julie Brahmer, MD, said at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

"Durable clinical benefit was see in both squamous and nonsquamous non-small cell lung cancer," said Brahmer of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University. "These findings support the importance of the PD-1 pathway in non-small cell lung cancer therapy across different histologies."

Relatively little information has accumulated regarding the PD-1 pathway and its role in NSCLC and other solid tumors. Brahmer briefly summarized what is known about the pathway.

PD-1 expression on tumor-infiltrating lymphocytes in NSCLC correlates with decreased cytokine production and effector function. Increased PD-L1 expression on tumor cells correlates with a decrease in the number of tumor-infiltrating lymphocytes in the same region.

Results of a phase I study of BMS-936558 suggested that PD-L1 expression might predict response to anti-PD-1 therapy.

Brahmer and colleagues continued the investigation of BMS-936558 in a phase I dose-finding study involving patients with heavily pretreated NSCLC (as many as five prior regimens). The vast majority (94%) of the patients had undergone platinum-based chemotherapy and 34% had a prior tyrosine kinase inhibitor.

All patients initially received an 8-week course of the antibody, and study participants who had stable disease or better response continued to an expansion phase.

Investigators randomized patients to 1, 3, or 10 mg/kg of the antibody, and treatment continued until disease progression or development of unacceptable toxicity. Brahmer reported safety data for 122 patients and efficacy data for 76 patients.

In general, the anti-IgG4 antibody was well tolerated, and the maximum tolerated dose had not been reached at the 10 mg/kg level. Investigators saw no evidence of a relationship between dose and frequency of adverse events.

There were two drug-related deaths because of pulmonary toxicity and both were due to pneumonitis.

Of the patients evaluable for response, one of 18 patients in the 1 mg/kg cohort had a partial response, as did six of 19 in the 3 mg/kg cohort, and seven of 39 in the 10 mg/kg group. Additionally, one patient had stable disease for at least 24 weeks with the lowest dose, as did two patients at each of the two higher doses.

Six patients with squamous tumors had partial responses (33%) and one had stable disease. Partial responses occurred in seven patients with nonsquamous histology (12.5%). Five patients with nonsquamous histology had stable disease lasting at least 24 weeks (7%).

Three patients had a persistent decrease in overall tumor burden but in the presence of new lesions so they were not considered responders, the authors explained.

Analysis of pretreatment tumor specimens obtained from 42 patients showed that responses occurred only in patients who had PD-L1-positive tumors, consistent with data from the earlier phase I trial.

The study was supported by Bristol-Myers Squibb (BMS) and investigators in the study included company employees.

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